Pathogenic microorganisms, including viruses, bacteria, fungi, and protozoans, may cause infections on any bodily surface, either externally on the skin or mucosal surface or internally in the blood or interior tissues.
For example, in otolaryngology, an acute or chronic sinusitis caused by pathogenic microorganisms in the paranasal sinuses is a common problem. Typically, acute bacterial infections are treated using standard antibiotic therapies. Chronic infections, on the other hand, are very difficult to control: a variety of systemic antimicrobial therapies have been proposed to clear such infections, and various surgical therapies are available for removing obstructions to mucosal outflow from the sinuses in order to improve ventilation of the cavities. Despite the large number of existing therapies, however, it is difficult to clear paranasal sinus infections, which often persist due to the presence of biofilms, persistent fluid and mucous collections, poor ventilation, and poor access to systemically delivered therapies.
Acute or chronic otitis media caused by pathogenic microorganisms in the middle ear usually results in a middle ear effusion that impairs hearing ability. Systemic antibiotics have poor penetration into the middle ear cavity and overuse of antibiotics in recurrent otitis media leads to increased antibiotic resistance. Surgical treatment involves placing pressure-equalizing tubes across the tympanic membrane to equalize the pressure in the middle-ear space and provide a channel for drainage of middle-ear effusions. These tubes, however, may also provide a path for pathogenic microorganisms to enter the middle ear cavity from the outside environment, thereby resulting in recurrence of otitis media after the tube placement.
Infections in or around a joint can also be difficult to treat. Joint spaces are typically sterile; orthopedic procedures in which joint spaces are intruded upon and subjected to placement of orthopedic implants may invite post-operative infection. This type of infection leads to serious complications in total joint arthroplasty procedures, for example, that often leads to explantation of the orthopedic implants and/or risk of the patient's health.
Accordingly, these conditions and diseases such as cystitis, periodontal disease, gastritis, vaginosis, esophagitis, colitis, dermatitis, acne, and dental caries remain challenging to treat. Additionally, traditional treatments using systemic antibiotics may provide drug exposure and side effects to areas distant from the site of infection, and are a possible cause of increasing anti-microbial resistance.
One treatment method for reducing infectious pathogens involves adding riboflavin (vitamin B2) to the site of infection or potential infection and exposing the site to ultraviolet (UV) light, which activates the riboflavin. The activated riboflavin chemically alters functional groups of nucleic acids (i.e., DNA and RNA) of the pathogens, thereby interfering with the pathogens' ability to replicate. Such targeted treatments may effectively treat the selected, diseased tissue and solve the difficulties of biofilm formation (in which pathogens form difficult-to-eradicate agglomerations) and subtherapeutic concentrations of systemically delivered antibiotics. These techniques, however, are at present only available for treating pathogenic infections on external anatomic surfaces (e.g., skin and skin structures) or deactivating pathogens in blood products. Additionally, the use of activated riboflavin remains primarily a sterilization technique, not a therapeutic modality. Very few laboratory-based, ex vivo sterilization techniques have in vivo, therapeutic applicability.
Consequently, there is a need for a therapeutic modality that can be applied to pathogen infected regions that are internal to the anatomy and difficult to access therapeutically.